Phosphorus (P) is essential for growth of all organisms, and P content is correlated with growth in most taxa. Although P content was initially considered to be a trait fixed at the species level, there is growing evidence for considerable intraspecific variation. Selection on such variation can thus alter the rates at which P fluxes through food webs. Nevertheless, prior work describing the sources and extent of intraspecific variation in P content were not genetically explicit, confounded by unknown genetic background and evolutionary history. We constructed an F2 recombinant population of the dominant freshwater grazer, Daphnia pulicaria to mitigate such issues. F2 recombinants exhibited considerable variation in growth rate, P content (0.49%-1.97%), P use efficiency (PUE; 51-208 mg biomass/mg P), and correlated traits such as hatching time of resting eggs, in common garden conditions. These results clearly demonstrate the scope of genetic recombination in generating variation in ecologically relevant traits. The absence of environmental selection is a likely component driving such variation not observed in natural settings. Although phosphoglucose isomerase (PGI) genotype was significantly associated with variation in hatching time of resting eggs, contrary to prior work with less rigorous designs, and allelic variation at the PGI locus did not explain variation in P content and PUE of Daphnia, indicating that such quantitative traits are under polygenic control. Together, these results suggest that although there is considerable genetic scope for variation in key ecologically relevant traits, such as P content and efficiency of P use, these traits are likely under strong stabilizing selection, most likely due to selection on growth rate and size. Importantly, our observations suggest that anthropogenic alterations to P supply due to eutrophication could alter selection on these traits, thereby rapidly altering the role Daphnia plays in the P cycle of lakes.Breast density is strongly associated with breast cancer risk; however, studies on the association between density changes and breast cancer risk have controversial results. The aim of our study was to determine the association between breast density changes and breast cancer risk in East-Asian women. We included 3?301?279 women aged ?40?years screened for breast cancer twice during 2009 to 2010 and 2011 to 2012. Data were obtained from the National Health Insurance Service (NHIS) database. Breast density was evaluated using the Breast Imaging-Reporting and Data System (BI-RADS). Relative risk (RR) and 5-year risk of developing breast cancer according to density category changes were calculated. Overall, 23.0% of the women had a higher breast density and 22.2% of the women had a lower breast density in second screening compared to the first. An increase in the BI-RADS density category between two subsequent mammographic screenings was associated with an increase in breast cancer risk and vice versa in terms of RR. The 5-year breast cancer risk was affected by the initial BI-RADS density category, changes in density category and patients' characteristics such as age, menopausal status and family history of breast cancer. In patients with breast cancer family history, the 5-year breast cancer risk was prominent, at a maximum of 2.39% (95% CI = 1.23-3.55) in women with breast density category of 2 to 4. Changes in the BI-RADS density category were associated with breast cancer risk. Longitudinal measures of BI-RADS density may be helpful in identifying high-risk women, especially those with a breast cancer family history.Mucosal associated invariant T (MAIT) cells are anti-microbial innate-like T cells that are abundant in blood and liver. MAIT cells express a semi-invariant T-cell receptor (TCR) that recognizes a pyrimidine ligand, derived from microbial riboflavin synthesis, bound to MR1. Both blood and liver derived (ld)-MAIT cells can be robustly stimulated via TCR or by cytokines produced during bacterial or viral infection. In this study, we compared the functional and transcriptomic response of human blood and ld-MAIT cells to TCR signals (Escherichia coli or the pyrimidine ligand) and cytokines (IL-12 + IL-18). While the response of blood and ld-MAIT cells to TCR signals were comparable, following cytokine stimulation ld-MAIT cells were more polyfunctional than blood MAIT cells. Transcriptomic analysis demonstrated different effector programmes of ld-MAIT cells with the two modes of activation, including the enrichment of a tissue repair signature in TCR-stimulated MAIT cells. https://www.selleckchem.com/ Interestingly, we observed enhancement of IL-12 signaling and fatty acid metabolism in untreated ld-MAIT cells compared with blood MAIT cells. Additionally, MAIT cells from blood and liver were modulated similarly by TCR and cytokine signals. Therefore, we report that blood and ld-MAIT cells are fundamentally different but undergo conserved changes following activation via TCR or by cytokines.Integrins are heterodimeric transmembrane proteins that play important roles in various biological processes. Most integrins serve as adhesion molecules and transmit bidirectional signaling across the cell membrane through global conformational changes from the bent closed to the extended open conformation. However, integrin β8 is distinctive in structure and function. Its cytoplasmic domain lacks the conserved protein-binding sequence, which is important in transmitting inside-out signals, suggesting that integrin β8 may have a different activation mechanism or lack such signaling. In addition, the ligand-binding or activating metal ion Mn2+ does not induce a global conformational change in integrin β8 . It may have only one conformation, that is, an extended, closed conformation, but with high affinity for ligands under physiological conditions, and is, therefore, considered an atypical integrin member. The extended structure and high ligand-binding affinity of integrin αv β8 make it ideal for encountering and binding ligands expressed on an opposing cell or in the extracellular matrix. In this review, we summarize the progress in integrin β8 research with a focus on its distinctive function and structure among integrin members.